The goal of this research is to understand nuclear transport, the mechanism by which macromolecules such as proteins and RNAs move into and out of the nucleus. This critical cellular process is essential for maintaining cells in a normal growth state so that they do not become transformed and cause uncontrolled or cancerous growth. For example, many aspects of cell growth are regulated by transcription factors that are transported into the nucleus in a signal-dependent manner. Finally, a more detailed understanding of the mechanisms that govern export of RNA from the nucleus may lead to improved anti-viral therapies. The proposed research employs the budding yeast Saccharomyces cerevisiae as a model system. S. cerevisiae serves as an ideal system because all the components that mediate nuclear transport have been extremely well- conserved through evolution. The use of this model system allows us to employ a multi-faceted approach that combines genetics, cell biology, biochemistry, and structural studies to address the complicated questions that must be understood in order to understand the detailed mechanism of nucleocytoplasmic transport.